The present invention relates to processes and intermediates for the preparation of azabicyclo[2.2.2]octan-3-imines which in turn are intermediates for the preparation of substituted 2-diphenylmethyl-N-phenylmethyl-1-azabicyclo[2.2.2]octan-3-amino compounds having Substance P antagonizing properties ("the final compounds"). The invention also relates to phenylmethylene imine intermediates for making the azabicyclo[2.2.2]octan3-imines and to a process for making them. The invention further relates to a process for preparing the cis-compounds of the final compounds from the azabicyclo[2.2.2]octan-3-imines, and a process for resolving a racemic mixture of the cis-compound.
The final compounds, a process for their preparation, and their ability to antagonize Substance P are described in International Publication WO 90/05729. These compounds are of use in the treatment of diseases caused by an excess of Substance P. Substance P is a naturally occurring undecapeptide belonging to the tachykinin family of peptides, the latter being so-named because of their prompt stimulatory action on smooth muscle tissue. More specifically, substance P is a pharmacologically-active neuropeptide that is produced in mammals (having originally been isolated from gut) and possesses a characteristic amino acid sequence. The wide involvement of substance P and other tachykinins in the pathophysiology of numerous diseases has been amply demonstrated in the art. Examples of such diseases are psychosis, migraine, rheumatoid arthritis and ulcerative colitis.